Regulation of the interferon-inducible 2'-5'-oligoadenylate synthetases by adenovirus VA(I) RNA. 2012

Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
Department of Chemistry, University of Manitoba, Parker Building, 144 Dysart Road, Winnipeg, Manitoba, Canada R3T 2N2.

Foreign double-stranded RNA (dsRNA) generated during the normal course of the viral life cycle serves as a key infection recognition element by proteins of the innate immune response. To circumvent this response, all adenoviruses synthesize at least one highly structured RNA (VA(I)), which, after processing by the RNA silencing machinery, inhibits the innate immune response via a series of interactions with specific protein partners. Surprisingly, VA(I) positively regulates the activity of the interferon-induced 2'-5'-oligoadenylate synthetase (OAS) enzymes, which typically represent a key mechanism whereby host-cell protein translation is attenuated in response to foreign dsRNA. We present data investigating the regulation of the OAS1 isoform by VA(I) derivatives and demonstrate that a processed version of VA(I) lacking the terminal stem behaves as a pseudo-inhibitor of OAS1. A combination of electrophoretic mobility shift assays, dynamic light scattering, and non-denaturing mass spectrometry was used to quantitate binding affinity and characterize OAS1:VA(I) complex stoichiometry. Enzyme assays characterized the ability of VA(I) derivatives to activate OAS1. Finally, the importance of RNA 5'-end phosphorylation state is investigated, and it emphasizes its potential importance in the activation or inhibition of OAS enzymes. Taken together, these data suggest a plausible strategy whereby the virus produces a single RNA transcript capable of inhibiting a variety of members of the innate immune response.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000256 Adenoviridae A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases. Adenoviruses,Ichtadenovirus,Adenovirus,Ichtadenoviruses
D012330 RNA, Double-Stranded RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms. Double-Stranded RNA,Double Stranded RNA,RNA, Double Stranded
D012367 RNA, Viral Ribonucleic acid that makes up the genetic material of viruses. Viral RNA
D013058 Mass Spectrometry An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers. Mass Spectroscopy,Spectrometry, Mass,Spectroscopy, Mass,Spectrum Analysis, Mass,Analysis, Mass Spectrum,Mass Spectrum Analysis,Analyses, Mass Spectrum,Mass Spectrum Analyses,Spectrum Analyses, Mass
D015088 2',5'-Oligoadenylate Synthetase An enzyme that catalyzes the conversion of ATP into a series of (2'-5') linked oligoadenylates and pyrophosphate in the presence of double-stranded RNA. These oligonucleotides activate an endoribonuclease (RNase L) which cleaves single-stranded RNA. Interferons can act as inducers of these reactions. 2',5'-Oligoadenylate Polymerase,2-5A Synthetase,(2'-5')An Polymerase,2',5'-Oligo(A) Polymerase,2',5'-Oligo(A) Synthetase,2,5 Oligoadenylate Polymerase,2,5 Oligoadenylate Synthetase,ATP-(2'-5')oligo(A)adenylyltransferase,2',5' Oligoadenylate Polymerase,2',5' Oligoadenylate Synthetase,Oligoadenylate Polymerase, 2,5,Oligoadenylate Synthetase, 2,5,Polymerase, 2',5'-Oligoadenylate,Polymerase, 2,5 Oligoadenylate,Synthetase, 2',5'-Oligoadenylate,Synthetase, 2,5 Oligoadenylate
D057131 Immune Evasion Methods used by pathogenic organisms to evade a host's immune system. Evasion, Immune,Evasions, Immune,Immune Evasions

Related Publications

Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
February 1995, The Journal of biological chemistry,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
November 1999, FEBS letters,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
January 2005, Methods in molecular medicine,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
January 2007, Cytokine & growth factor reviews,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
May 1999, Virology,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
August 1991, Journal of interferon research,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
May 1983, Molecular and cellular biology,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
July 2019, Wiley interdisciplinary reviews. RNA,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
September 2000, Journal of virology,
Hui Meng, and Soumya Deo, and Shawn Xiong, and Edis Dzananovic, and Lynda J Donald, and Cody W van Dijk, and Sean A McKenna
January 1984, The Journal of biological chemistry,
Copied contents to your clipboard!